Several medical applications utilizing genetic determinants have evolved in recent years. In such applications, the introduction of whole genes or specific nucleic acids into cells is of central importance. This process is often referred to as gene transfection independently of the origin of the cells, the sequence and character of the nucleic acid, and irrespective of whether the transfer is performed in vivo or ex vivo.
To facilitate the process of gene transfection several different approaches have been developed. Such approaches include among others i) using biological vectors (including viral vectors), ii) associating a nucleic acid with a cationic liposome, iii) associating a nucleic acid with peptides covalently linked to a transfection agent, and iv) coating minute gold particles by nucleic acids and using the coated particles for a bio-ballistic transfer.
The major iscom constituents are quillaja saponins and cholesterol. The procedure for preparation of iscoms comprises solubilization of amphipathic polypeptides in preferably nonionic detergents, addition of Quillaja saponins, cholesterol, and possibly also phosphatidylcholine. In the presence of amphipathic proteins, iscom particles are formed on removal of the detergent.
Morein (see e.g. U.S. Pat. No. 4,578,269) was the first to describe that iscoms not only formed a very characteristic structural complex, but also possessed significant immunogenic properties when amphipathic antigens were inserted into this complex by hydrophobic interaction. Conventional iscoms (immunostimulating complexes) have since been used for vaccine formulations and combine a multimeric presentation of an antigen with an adjuvant functionality. (see e.g. U.S. Pat. No. 6,080,725 to Marciani).